This invention relates to liquid sampling techniques and devices for taking accurate and reproducible liquid sample volumes, and in particular to a syringe drive with a lead screw mechanism for use in an autosampler system which itself may be used in conjunction with a liquid chromatograph.
In liquid chromatography systems, automated sampling equipment has been developed and used for analyzing multiple samples. Small volumes of liquid samples are automatically withdrawn from sample containers and then injected into liquid chromatography columns for separation and analysis. Such an automated mechanism is described in U.S. Pat. No. 4,622,457 to Bradley et al, issued Nov. 11, 1986, the disclosure of which is hereby incorporated by reference.
The trend in liquid chromatography analysis has been toward the use of smaller and smaller samples. Today, typical sample volumes may be in the range of 10-50 .mu.l, but may range down to as little as 1.0 .mu.l or less. With the small sample volumes analyzed, it has become critical that the sampling mechanism not only be accurate in the volume taken, but also produce reproducible results. That is, from one sample to the next, the sampling mechanism must be able to withdraw and deliver the same volume, or whatever volume is preselected, time after time.
A number of mechanisms have been used in the prior art for withdrawing samples from sample containers. These include both purge mechanisms and syringe mechanisms. Purge mechanisms operate by purging a sample loop. However, purge mechanisms tended to be uncontrolled. That is, gas pressurization or suction alone has been relied on to move a sample volume from its container into the sample loop. Generally, such mechanisms may be used with a complete fill loop only, where the sample taken completely filled a predetermined volume in a sample loop.
Syringe transport mechanisms have also been used to withdraw a sample volume from a container. Typically, the syringe is physically inserted into the sample container, a predetermined sample volume is drawn into the syringe, and the syringe is then removed from the sample container. The syringe containing the sample is then physically moved and connected to a sample injection mechanism for injecting the sample into a chromatography column or other separation device or detector. Newer syringe and automated sampler designs have utilized multiport valves so that the sample may be drawn directly into a sample loop by the syringe.
The use of a syringe to withdraw a sample offers the benefit of a low waste level. Only the small volume of sample needed is withdrawn. However, prior syringe mechanisms have had a number of problems which have affected accuracy and reproducibility. Generally, the syringe includes a plunger which is mechanically connected to a stepper motor through a lead screw drive mechanism. Lead screw mechanisms have not provided perfectly linear motion, due either to slight manufacturing defects such as a bent lead screw or misalignment occurring during assembly or in use. Rather, typically there is a cyclic modulation of the linear displacement of the mechanism.
With the advent of sample volumes of only a fraction of a microliter, less than one complete rotation of the screw drive is needed. Thus, for a 0.5 .mu.l sample, the screw drive may turn less than one-quarter of a full rotation. Any misalignment of the screw drive with respect to the plunger, even if small, may introduce significant errors into the sample volume and/or the ability to reproduce the same sample volume repeatedly. This increases the costs of manufacturing and assembling the syringe drive because of the need for strict tolerances to minimize any misalignment. Moreover, over time, the drive mechanism will wear and introduce an additional degree of wobble or misalignment. Even if perfectly aligned initially, the mechanism may become misaligned through movement of equipment and the concomitant bumping and jarring of the mechanism which is inevitable during use. Misalignment also increases stress on the mechanism which may result in excess wear.
While it may be possible to attempt to use lead screw mechanisms having a much greater number of threads per inch to improve accuracy during operation, such screws may be prohibitively expensive to manufacture and may themselves include small manufacturing defects. However, misalignment would remain a problem. Accordingly, there is a need in the art for a relatively simple and inexpensive syringe drive with a lead screw mechanism which permits both accurate and reproducible sample withdrawals.